The preparation of steroids such as chenodeoxycholic acid, 25-hydroxycholesterol and 1.alpha.,25-dihydroxycholesterol, the last two compounds being useful intermediates for the preparation of Vitamin D.sub.3 metabolites, has involved numerous problems. For example, in the past, it has been necessary to utilize procedures involving many preparative steps, thereby resulting in low overall yields of the ultimate product. Additionally, the synthetic procedures have been time-consuming and tedious, involving the need for separation of various products by chromatographic procedures in order to arrive at a substrate having the natural steroid configuration at the 20-position. Because of the foregoing problems, it has heretofore been impractical to prepare these compounds of potential commercial importance on a commercially-practical scale.
17-keto steroids, such as dehydroepiandrosterone, are available from microbial degradation of readily-available plant steroids such as sitosterol, campesterol, etc. Thus, the 17-keto steroids are abundantly-available substrates which could provide attractive starting materials for the synthesis of a number of steroid compounds which are of potential, commercial importance. For example, 17-keto steroids can be hydroxylated microbially, thereby eliminating time-consuming preparative steps which are normally associated with the construction of a suitable substrate. However, there has heretofore been no methodology available for the efficient stereospecific introduction of a side chain at the 17-position having the natural steroid C-20 configuration which would allow for further elaboration of these substrates into commercially-important products.
The ene reaction, which is known in the prior art, involves the addition of a compound with a double bond (enophile) to an olefin possessing an allylic hydrogen (ene) and involves allylic shift of the double bond, transfer of the allylic hydrogen to the enophile and bonding between the two unsaturated termini. It is also known in the prior art that 17-keto steroids may be modified by reaction with an ethyltriphenylphosphonium halide to produce 17-ethylidene derivatives having a Z-double bond configuration.